Limited data exist about combination anti-HIV treatment regimens in children, including how those drugs are cleared by the body in children. The purpose of this study is to measure the blood levels of the following combinations of anti-HIV drugs in HIV infected chilren: tenofovir disoproxil fumurate (TDF) and efavirenz (EFV) or nevirapine (NVP); TDF and darunavir (DRV) with or without EFV; and TDF and ritonavir (RTV) with or without EFV.

Intensive PK study will occur at least once. This will require a 24-hour inpatient visit.

Other Name: PK Study

Experimental: E

TDF and DRV with or without EFV throughout study

Drug: Darunavir

300 mg or 600 mg orally twice daily

Other Name: DRV

Drug: Efavirenz

Dosage dependent on participant

Other Name: EFV

Drug: Ritonavir

50 mg or 100 mg orally twice daily

Other Name: RTV

Drug: Tenofovir disoproxil fumarate

300 mg orally daily

Other Name: TDF

Procedure: Pharmacokinetic Study

Intensive PK study will occur at least once. This will require a 24-hour inpatient visit.

Other Name: PK Study

Experimental: F

TDF and ATV and RTV with or without EFV throughout study

Drug: Atazanavir

200 mg to 400 mg orally daily

Other Name: ATV

Drug: Efavirenz

Dosage dependent on participant

Other Name: EFV

Drug: Ritonavir

50 mg or 100 mg orally twice daily

Other Name: RTV

Drug: Tenofovir disoproxil fumarate

300 mg orally daily

Other Name: TDF

Procedure: Pharmacokinetic Study

Intensive PK study will occur at least once. This will require a 24-hour inpatient visit.

Other Name: PK Study

Detailed Description:

Because all of the available non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs) are metabolized by and affect hepatic cytochrome enzymes, combinations of two or more of these drugs produce complex pharmacokinetic (PK) interactions. However, little data exist regarding PK of anti-HIV drug combinations in the pediatric population. The purpose of this study is to assess steady-state PK of the following anti-HIV regimens: TDF and EFV or NVP; TDF and DRV with or without EFV; and TDF and RTV with or without EFV. In addition, this study will evaluate how age, length of treatment, adverse effects, and genes affect children's response to different anti-HIV combinations.

This study will last between 1 and 7 weeks. Participants in this study will be grouped based on the treatment regimen they are receiving or about to initiate. There are three groups in this study. Group D participants will receive TDF and EFV or NVP; Group E participants will receive TDF and DRV with or without EFV; and Group F participants will receive TDF and RTV with or without EFV. The inclusion of EFV or NVP will be dependent on each participant's prescribed regimen. Participants within each group will be stratified by age and how long they have been receiving their anti-HIV regimens. Antiretrovirals will not be provided by this study.

Most participants will have two study visits. The first visit will occur at study entry. Medical history, a physical exam, and blood collection will occur. The second visit will occur within 35 days of study entry and will take approximately 24 hours. Blood collection for PK studies, a physical exam, and medical history will be done at this visit. Urine collection will occur at all visits for female participants.

Participants will undergo PK testing at least 14 days after initiating their study regimens. Participants will be given a dose of their anti-HIV medications with food. A blood sample will be taken before dosing. Blood samples will also be taken at 1, 2, 4, 6, 8, 12, and 24 hours after dosing. Participants in Groups E and F may need to repeat PK testing within 6 weeks of initial PK testing at the discretion of the investigator.

Eligibility

Ages Eligible for Study:

8 Years to 17 Years

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Criteria

Note: The original Groups A, B, and C have been removed, and Groups D, E, and F have been added per protocol amendment dated 11/16/07.

Inclusion Criteria:

HIV infected

Currently receiving or about to initiate one of the following anti-HIV regimens: TDF with EFV or NVP, TDF and DRV/r with or without EFV, or TDF with ATV/r with or without EFV

Body surface area at least 0.85 m2

Parent or guardian willing and able to provide signed informed consent

Willing to use acceptable forms of contraception

Exclusion Criteria:

Liver disease that may affect the metabolism of study drugs

Certain abnormal laboratory values

Require certain medications

Treatment with any anti-HIV or nonantiretroviral drug that could interact with drugs under PK study in the 14 days prior to study entry

Any clinical or laboratory toxicity of Grade 4 or higher at screening. More information on this criterion can be found in the protocol.

Pregnant or breastfeeding

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00260078